Bregje van Oorschot1, Suzanne E Hovingh2, Perry D Moerland3, Jan Paul Medema2, Lukas J A Stalpers2, Harry Vrieling4, Nicolaas A P Franken2. 1. Laboratory for Experimental Oncology and Radiobiology (LEXOR), Center for Molecular Medicine (CEMM), Department of Radiation Oncology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. Electronic address: b.vanoorschot@amc.uva.nl. 2. Laboratory for Experimental Oncology and Radiobiology (LEXOR), Center for Molecular Medicine (CEMM), Department of Radiation Oncology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. 3. Bioinformatics Laboratory, Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. 4. Department of Toxicogenetics, Leiden University Medical Center, Leiden, The Netherlands.
Abstract
PURPOSE: To investigate clinical parameters and DNA damage response as possible risk factors for radiation toxicity in the setting of prostate cancer. METHODS AND MATERIALS: Clinical parameters of 61 prostate cancer patients, 34 with (overresponding, OR) and 27 without (non-responding, NR) severe late radiation toxicity were assembled. In addition, for a matched subset the DNA damage repair kinetics (γ-H2AX assay) and expression profiles of DNA repair genes were determined in ex vivo irradiated lymphocytes. RESULTS: Examination of clinical data indicated none of the considered clinical parameters to be correlated with the susceptibility of patients to develop late radiation toxicity. Although frequencies of γ-H2AX foci induced immediately after irradiation were similar (P=.32), significantly higher numbers of γ-H2AX foci were found 24 hours after irradiation in OR compared with NR patients (P=.03). Patient-specific γ-H2AX foci decay ratios were significantly higher in NR patients than in OR patients (P<.0001). Consequently, NR patients seem to repair DNA double-strand breaks (DSBs) more efficiently than OR patients. Moreover, gene expression analysis indicated several genes of the homologous recombination pathway to be stronger induced in NR compared with OR patients (P<.05). A similar trend was observed in genes of the nonhomologous end-joining repair pathway (P=.09). This is congruent with more proficient repair of DNA DSBs in patients without late radiation toxicity. CONCLUSIONS: Both gene expression profiling and DNA DSB repair kinetics data imply that less-efficient repair of radiation-induced DSBs may contribute to the development of late normal tissue damage. Induction levels of DSB repair genes (eg, RAD51) may potentially be used to assess the risk for late radiation toxicity.
PURPOSE: To investigate clinical parameters and DNA damage response as possible risk factors for radiation toxicity in the setting of prostate cancer. METHODS AND MATERIALS: Clinical parameters of 61 prostate cancerpatients, 34 with (overresponding, OR) and 27 without (non-responding, NR) severe late radiation toxicity were assembled. In addition, for a matched subset the DNA damage repair kinetics (γ-H2AX assay) and expression profiles of DNA repair genes were determined in ex vivo irradiated lymphocytes. RESULTS: Examination of clinical data indicated none of the considered clinical parameters to be correlated with the susceptibility of patients to develop late radiation toxicity. Although frequencies of γ-H2AX foci induced immediately after irradiation were similar (P=.32), significantly higher numbers of γ-H2AX foci were found 24 hours after irradiation in OR compared with NR patients (P=.03). Patient-specific γ-H2AX foci decay ratios were significantly higher in NR patients than in OR patients (P<.0001). Consequently, NR patients seem to repair DNA double-strand breaks (DSBs) more efficiently than OR patients. Moreover, gene expression analysis indicated several genes of the homologous recombination pathway to be stronger induced in NR compared with OR patients (P<.05). A similar trend was observed in genes of the nonhomologous end-joining repair pathway (P=.09). This is congruent with more proficient repair of DNA DSBs in patients without late radiation toxicity. CONCLUSIONS: Both gene expression profiling and DNA DSB repair kinetics data imply that less-efficient repair of radiation-induced DSBs may contribute to the development of late normal tissue damage. Induction levels of DSB repair genes (eg, RAD51) may potentially be used to assess the risk for late radiation toxicity.
Authors: Sayeda Yasmin-Karim; Bashkim Ziberi; Johanna Wirtz; Noella Bih; Michele Moreau; Romy Guthier; Victoria Ainsworth; Juergen Hesser; G Mike Makrigiorgos; Michael D Chuong; Xiao Wei; Paul L Nguyen; Wilfred Ngwa Journal: Int J Radiat Oncol Biol Phys Date: 2021-09-13 Impact factor: 7.038
Authors: Pavel Lobachevsky; Trevor Leong; Patricia Daly; Jai Smith; Nickala Best; Jonathan Tomaszewski; Ella R Thompson; Na Li; Ian G Campbell; Roger F Martin; Olga A Martin Journal: Cancer Lett Date: 2016-09-28 Impact factor: 8.679
Authors: Carsten Herskind; Christopher J Talbot; Sarah L Kerns; Marlon R Veldwijk; Barry S Rosenstein; Catharine M L West Journal: Cancer Lett Date: 2016-03-02 Impact factor: 8.679
Authors: Antje Fahrig; T Koch; M Lenhart; P Rieckmann; R Fietkau; Luitpold Distel; B Schuster Journal: Strahlenther Onkol Date: 2017-09-08 Impact factor: 3.621
Authors: Cholpon S Djuzenova; Marcus Zimmermann; Astrid Katzer; Vanessa Fiedler; Luitpold V Distel; Martin Gasser; Anna-Maria Waaga-Gasser; Michael Flentje; Bülent Polat Journal: BMC Cancer Date: 2015-11-06 Impact factor: 4.430
Authors: Mohammad Habash; Luis C Bohorquez; Elizabeth Kyriakou; Tomas Kron; Olga A Martin; Benjamin J Blyth Journal: Cancers (Basel) Date: 2017-10-27 Impact factor: 6.639